In general, a “chiral” object is one that is not superimposable upon its mirror image. In other words, a chiral object and its mirror image are similar in constitution or content, but different in orientation. Examples of chiral objects include a human hand, a mechanical screw, or a propeller. While they the mirror images look similar, they have different characteristic orientations with regard to their parts (e.g., the digits on the hand, the helical orientation of the screw, and the pitch orientation of the blades on the propeller).
In stereochemistry, two forms of a chiral object (such as a molecule) are also known as enantiomers, which is a type of stereoisomer. Enantiomers have the same chemical purity (e.g., the same mass, absorbance, refractive index, Verdet constant, etc.) but have different configurations in symmetry or symmetric properties. A collection containing only one enantiomeric form of a chiral molecule is often referred to as enantiopure, enantiomerically pure, or optically pure. However, unlike other stereoisomers, enantiomers are often difficult to separate and quantitate.
Detection of chiral molecules has become of increasing interest to the pharmaceutical industry over the last twenty years. This interest is driven at least in part by the common occurrence of drastically different pharmacological activities between enantiomers. The different pharmacological activity associated between enantiomers often requires that the drug be produced as a single chiral isomer. This single chiral isomer would be selected as it would have the most beneficial effects or, in some cases, would not have dangerous pharmacological activity. However, analytical methods for assaying enantiomeric purity have not kept pace with the increasing demands for rapid, high sensitivity, enantiomeric analysis. To date no generally applicable method for high throughput enantiomeric purity screening is available to the researcher.
There are known improvements to chiral analysis techniques, more specifically, in the area of reducing noise associated with the measurement of the additional optical rotation induced by a chiral sample. Single beam methods utilizing electronic or optical means to filter noise are quite common (see, for example, WO 01/06918). Other known methods utilize dual beams either by comparison to a reference cell (U.S. Pat. No. 4,912,059), mixing out of phase sinusoidal signals (U.S. Pat. No. 5,477,327), switching between a signal and reference beam (U.S. Pat. No. 5,621,528), or using a two frequency laser source with two orthogonal linear polarized waves (U.S. Pat. Nos. 5,896,198 and 6,327,037). These methods attempt to determine the displacement from the null point of optical transmission.
It is also known to use pockels cell modulation for differential chiral analysis in flow cells (U.S. Pat. No. 5,168,326). This technology involves the application of oscillating voltage to the pockels cell to produce alternating beams of linearly polarized light and circularly polarized light. By subtracting the rotation angles calculated for both beams, common sources of noise are effectively canceled out, giving a more sensitive measurement.
Thus, there remains a need for systems and methods that more accurately determine the chiral purity of a sample.